Gemini curcumin inhibits 4T1 cancer cell proliferation and modulates the expression of apoptotic and metastatic genes in Balb/c mice model

Background: Despite the attractive anti-cancer effects, poor solubility and low bioavailability have restricted the clinical application of Curcumin. Recent findings show that Gemini nano-curcumin (Gemini-Cur) significantly improves the cellular uptake of Curcumin and its anti-cancer effect in tumor cells. Here, we aimed to assess the suppressive effect of Gemini-Cur on 4T1 breast cancer cells in vitro and, subsequently, in BALB/c mouse models. Materials and methods: Fluorescence microscopy was employed to visualize cellular uptake and morphological changes of 4T1 cells during treatment with Gemini-Cur and void curcumin. MTT and annexin V/FITC assays were performed to study the toxic effect of Gemini-Cur on mouse cancer cells. For in vivo studies, BALB/c tumorbearing mice were used to evaluate the inhibitory effect of Gemini-Cur in comparison with mice receiving free Curcumin and nanoparticles. Results: Our data showed that Gemini-Cur enters the cells and inhibits proliferation in a time- and dosedependent manner. Annexin V/FITC confirmed apoptotic effect on 4T1 cells. In vivo studies also illustrated that tumor growth is suppressed in Gemini-Cur treated mice rather than controls. Expression studies demonstrated the modulation of apoptotic and metastatic genes, including Bax, Bcl-2, MMP-9, VEGF, and COX-2 in treated mice. Conclusion: In conclusion, these data demonstrate the promising anti-cancer properties of Gemini-Cur on mice models. However, further studies at molecular and cellular levels are required to conclude this therapeutic advantage.